Clinical Outcomes of Next-Generation Microwave Thermosphere Ablation for Hepatocellular Carcinoma with Primarily Hepatitis-Related Etiology.

BACKGROUND AND AIM: We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). METHODS: A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. We defined the following areas of the liver as those where MTA therapy is difficult to perform: caudate lobe and areas near the primary and secondary branches of the intrahepatic portal vein, inferior vena cava, gallbladder, heart, duodenum, abdominal esophagus, collateral veins around the liver, and spleen. Factors which predisposed patients to local tumor recurrence in the context of tumor location and complications were examined. RESULTS: The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0-21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: 6.6%, 13.8%, and 29.4% at three years in the ≤20 mm group (n = 483), 20-30 mm group (n = 107), and ≥30 mm group (n = 17), respectively (p < 0.001). The cumulative local tumor recurrence rate was similar despite difficult-to-treat status (p = 0.169). In the multivariable analysis, tumor size (>15 mm) (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.11-4.16; p = 0.023) and ablative margin (<3 mm) (HR, 2.94; 95% CI, 1.52-5.71; p = 0.001) were significantly associated with local tumor recurrence. Only tumor size (>15 mm) (odds ratio, 3.41 95% CI, 1.53-7.84; p = 0.026) was significantly associated with complications. CONCLUSIONS: MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

Flattened 1D fragments of fullerene C60 that exhibit robustness toward multi-electron reduction.

Fullerenes are compelling molecular materials owing to their exceptional robustness toward multi-electron reduction. Although scientists have attempted to address this feature by synthesizing various fragment molecules, the origin of this electron affinity remains unclear. Several structural factors have been suggested, including high symmetry, pyramidalized carbon atoms, and five-membered ring substructures. To elucidate the role of the five-membered ring substructures without the influence of high symmetry and pyramidalized carbon atoms, we herein report the synthesis and electron-accepting properties of oligo(biindenylidene)s, a flattened one-dimensional fragment of fullerene C60. Electrochemical studies corroborated that oligo(biindenylidene)s can accept electrons up to equal to the number of five-membered rings in their main chains. Moreover, ultraviolet/visible/near-infrared absorption spectroscopy revealed that oligo(biindenylidene)s exhibit enhanced absorption covering the entire visible region relative to C60. These results highlight the significance of the pentagonal substructure for attaining stability toward multi-electron reduction and provide a strategy for the molecular design of electron-accepting π-conjugated hydrocarbons even without electron-withdrawing groups.

Decrease in Ocular Blood Flow Thirty Minutes After Intravitreal Injections of Brolucizumab and Aflibercept for Neovascular Age-Related Macular Degeneration.

Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept are used widely to treat neovascular age-related macular degeneration (nAMD); however; they may theoretically affect the ocular blood flow. We investigated the short-term changes in the ocular blood flow between eyes with nAMD treated with intravitreal brolucizumab injections (IVBr) and intravitreal aflibercept injections (IVA). Methods: This study included 21 eyes of 21 Japanese patients with nAMD treated with either IVBr or IVA at Kurume University Hospital from April 2021 through June 2022. The rates of ocular blood flow at the optic nerve head (ONH mean blur rate [MBR]-vessel) and at the choroid (CHOR MBR) were analyzed before and 30 minutes after injections using laser speckle flowgraphy. Results: In the IVBr-treated group, the ONH MBR-vessel and CHOR MBR rates decreased significantly by 10.6% and 16.9% from baseline to 30 minutes after IVBr, respectively. In the IVA-treated group, ONH MBR-vessel and CHOR MBR rates decreased significantly by 9.4% and 6.1% from baseline to 30 minutes after IVA, respectively. There was no significant difference in the rates of decrease in the ONH MBR-vessel or CHOR MBR between the IVBr-treated and IVA-treated groups. Conclusion: Intravitreal injections of brolucizumab and aflibercept in eyes with nAMD cause significant decreases in ocular blood flow at the ONH and the choroid 30 minutes after injection. The rate of decrease in ocular blood flow was not significant between the eyes treated with brolucizumab and aflibercept. However, 3 of 10 eyes treated with brolucizumab but none of 11 eyes treated with aflibercept had more than a 30% decrease in the ocular blood flow at the choroid 30 minutes after injection.

Characteristics of hepatocellular carcinoma in patients with hepatitis C virus who received direct-acting antiviral therapy and achieved sustained virological response: The impact of a hepatologist on surveillance.

Background and Aim: The relationship between the characteristics of hepatocellular carcinoma (HCC) diagnosed after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy and surveillance status has not been sufficiently investigated. This study investigated the clinical risk factors for HCC development and HCC characteristics according to which type of physician performed follow-up after SVR. Methods: A total of 1070 patients in whom hepatitis C virus (HCV) was eradicated with DAA therapy were evaluated. Results: There were 458 patients followed by hepatologists (specialist group) and 612 followed by non-hepatologists (non-specialist group) after SVR. During the follow-up period, 54 patients developed HCC. The 1-, 2-, 3-, 4-, and 5-year cumulative incidence rates of HCC were 1.8, 4.1, 6.9, 10.5, and 17.2%, respectively. Multivariate Cox proportional hazards analysis showed that male sex (hazard ratio [HR], 3.139; 95% confidence interval [CI], 1.732-5.690), α-fetoprotein level (HR, 1.056; 95% CI, 1.035-1.077), and fibrosis-4 (FIB-4) index (HR, 1.051; 95% CI, 1.017-1.085) were significantly associated with HCC development, while the follow-up physician type after SVR was not. There were 25 patients with stage I HCC, 17 with stage II, 9 with stage III, and 3 with stage IV. Multivariate ordinal logistic regression showed that follow-up physician type (non-specialist) (HR, 39.100; 95% CI, 9.350-224.00) was independently associated with HCC stage, while α-fetoprotein level and FIB-4 index were not. Conclusion: When patients have more risk factors for HCC development after SVR (i.e., male sex, elevated α-fetoprotein, or elevated FIB-4 index), they should be followed by a hepatologist for HCC surveillance.

Utilization and evaluation of Citrus natsudaidai peel waste as a source of natural food additives.

This study aims to obtain beneficial ingredients from Citrus natsudaidai (CN) peel waste. The yields of ingredients were 26.2-31.6 mg/g dried material (DM) in pectin, 466-581 mg/g DM in insoluble dietary fiber, 5.56-7.15 g/kg fresh material (FM) in the hexane extracts obtained from CN peels, 23.8-27.0 mg/g DM in naringin, and 8.30-10.2 mg/g DM in neohesperidin. A sensory evaluation and instrumental assays using an Electronic nose and Electronic tongue were performed to evaluate aqueous solutions flavored with 0.02% hexane extracts obtained from CN peels. CN-flavored solutions had a preferred smell over commercial citrus-flavored drinks and were classified into the same group as commercial citrus juices in the Electronic nose assay. In addition, CN-flavored solutions showed sourness, bitterness, and orange-like taste, and the overall acceptance of CN-flavored solutions did not significantly differ from commercial citrus-flavored drinks. CN peel waste can be industrially utilized as a source of natural food additives.

Visual Outcomes and Prognostic Factors of Large Submacular Hemorrhages Secondary to Polypoidal Choroidal Vasculopathy.

PURPOSE: Patients with polypoidal choroidal vasculopathy (PCV) may develop large submacular hemorrhages (SMHs), which may result in severe visual loss. This study was performed to determine the visual outcomes and prognostic factors of large SMHs secondary to PCV. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients diagnosed with PCV who developed a large SMH. The best-corrected visual acuity (BCVA) data were collected at the SMH development, 1 month, 1 year after the SMH development, and at the final visit. Patients' medical information also were collected and included age, gender, systemic hypertension, current regular use of an anticoagulant or antiplatelet medication, the initial area of the SMH, breakthrough vitreous hemorrhage, ocular treatment, and fellow eye status. Univariate and multiple regression analyses were performed to determine the prognostic factors for the BCVA 1 year after the development of large SMHs. RESULTS: Thirty eyes of 29 patients were included in this study. The mean area of the SMHs at the development was 17.0 disc areas. The mean follow-up period after the development of SMHs was 53.5 months. The mean BCVA at the development, 1 month, and 1 year after the development, and at the final visit were 20/151, 20/263, 20/138, and 20/152, respectively. Multiple regression analyses indicated that a SMH 20 disc areas or larger was a significant negative factor, and the BCVA 1 month after the development was a significant positive factor affecting the BCVA 1 year after the development of large SMHs. CONCLUSION: The increase in the initial area of SMH was correlated inversely with the BCVA 1 year after the development of SMH. The BCVA 1 month after the development may predict the BCVA 1 year after the development of a large SMH.

FOLFIRINOX for Advanced Pancreatic Cancer Patients After Nab-Paclitaxel Plus Gemcitabine Failure.

OBJECTIVES: There is no standard chemotherapy for advanced pancreatic cancer (APC) after gemcitabine plus nab-paclitaxel (GP) failure. The aim of this study was to evaluate the efficacy and safety of FOLFIRINOX (5-Fluorouracil, leucovorin, irinotecan, and oxaliplatin) (5-Fluorouracil, leucovorin, irinotecan, and oxaliplatin) (FFX) and modified FFX (mFFX) for APC patients after GP failure. METHODS: We retrospectively evaluated the efficacy and safety of FFX in APC patients who were refractory or intolerant of GP. RESULTS: Between July 2014 and October 2018, 23 patients received FFX after failure of GP. The overall response rate (RR) was 23%, and the disease control rate (DCR) was 68%. The median progression-free survival (PFS) was 5.3 months (95% confidence interval, 2.5-8.9), and the median overall survival (OS) was 12.1 months (95% confidence interval, 4.0-14.2). Twelve patients received FFX, and 11 patients received mFFX. In the FFX group, the RR was 9%, the DCR was 73%, the PFS was 5.3 months, and the OS was 6.9 months. In the mFFX group, the RR was 23%, the DCR was 64%, the PFS was 4.3 months, and the OS was 12.8 months. There was no significant difference between the groups. CONCLUSIONS: FOLFIRINOX has potential activity for patients with APC in whom GP failed.

Proximate composition and profiles of free amino acids, fatty acids, minerals and aroma compounds in Citrus natsudaidai peel.

Bulky hard peel of Citrus natsudaidai is discarded and not utilized enough in Japan. In this study, the nutritional composition and volatile components of three cultivars of C. natsudaidai peel were determined. Considering the proximate composition and minerals, C. natsudaidai peels showed good carbohydrate and potassium content. The peel color varied probably due to the difference of cultivars. C. natsudaidai peels were extracted and analyzed for free amino acids and for fatty acids and volatile compounds. The amount of free amino acids in the extracts was not enough to affect the taste of extracts. The proportion of individual fatty acid was not comparable to other plant oils, however, typical aroma compounds with citrusy smell were identified. C. natsudaidai extracts could contribute for the utilization as flavoring additives without affecting taste.